Cyclic hydroxamic acids as antihypertensive agents

ABSTRACT

Method of treating hypertension by administering to a hypertensive patient a therapeutically effective amount of a compound of the Formula   WHEREIN R1, R2, and R3 each are hydrogen, alkyl, cycloalkyl or aryl.

United States Patent Jones et al.

[ CYCLIC HYDROXAMIC ACIDS AS ANTIHYPERTENSIVE AGENTS [75] Inventors: Peter Hadley Jones, Lake Forest;

Yvonne Connolly Martin, Waukegan, both of I11.

[73] Assignee: Abbott Laboratories, North Chicago, Ill.

22 Filed: Feb. 20, 1973 211 App]. No.: 333,600

Related US. Application Data [62] Division of Ser. No. 201,176, Nov. 22, 1971, Pat. No.

[52] US. Cl 424/263; 424/250 [51] Int. Cl A6lk 27/00 [58] Field of Search 424/250, 256, 263

[451 July 15,1975

[56] References Cited UNITED STATES PATENTS 2,666,054 1/1954 Safir 260/250 Primary Examiner-Stanley L Friedman Assistant ExaminerDaren M. Stephens Attorney, Agent, or Firm-Robert L. Niblack [57] ABSTRACT Method of treating hypertension by administering to a hypertensive patient a therapeutically effective amount of a compound of the Formula wherein R R and R each are hydrogen, alkyl, cycloalkyl or aryl.

1 Claim, No Drawings CYCLIC HYDROXAMIC ACIDS AS ANTII-IYPERTENSIVE AGENTS This is a division of application Ser. No. 201,176 filed Nov. 22, 1971 now U.S. Pat. No. 3,720,768.

DETAILED DESCRIPTION OF THE INVENTION This invention relates to a method of treating hypertension using cyclic hydroxamic acids as the antihypertensive agents.

Aspergillic acid and a number of its derivatives have been previously reported as anti-bacterial agents and some of the compounds have additionally been reported to possess antiinflammatory activity. It has now unexpectedly been found that the compounds are useful as antihypertensive agents.

The compounds useful in the practice of this invention are represented by the formula See, for example, Dunn et al., Pyrazine Derivatives XI Synthesis of Cyclic I-Iydroxamic Acids Related to As pergillic Acid J. Chem. Soc., 1949, 2707-l2; U.S. Pat. No. 2,666,054; Great Britain No. 1,238,958; France No. 2,022,146 and Great Britain No. 1,238,106.

The antihypertensive activity of the compounds useful in the practice of this invention was first established in the spontaneously hypertensive rat using standard procedures. The compounds are effective as antihypertensive agents at dosages of from 60 to 200 mg./kg. of body weight daily.

In the practice of this invention, the compounds are administered to hypertensive patients, preferably by the oral route, in divided dosages, i.e., three to four times daily. They may also be co-administered with, for example, diuretics or tranquilizers in treating hypertension.

While the compounds can be administered alone, that is, as the sole component of a filled capsule, it is preferred to formulate the compound in various dosage forms for oral or parenteral administration such as tablets, syrups, sterile aqueous or non-aqueous suspension and the like. The oral dosage forms are prepared by methods well known in the art (as are the parenteral) and generally include a pharmaceutically acceptable carrier or diluent such as lactose, starch or sucrose along with lubricating agents such as magnesium stearate and flavoring and sweetening agents and the like.

We claim:

1. A method of reducing blood pressure in hypertensive patients by administering a therapeutically effective amount of a compound of the formula wherein R R and R each are hydrogen, alkyl, cycloalkyl or aryl.

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. 3, 895, 114

DATED July 15, 1975 |NVENTOR(S) Peter Hadley Jones 6: Yvonne Connolly Martin It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

On the front page in the abstract, please delete R2 N OH 2 0 N a w 0 O H and substitute 1 3 lfi S 6 IJH In Column 2, Claim 1, please delete 1U 3 1 R N OH R and substitute Signed and Scaled this ninth D a) of December I 9 75 '[SEAL] Attest.

RUTH C. MASON Arresting Officer C. MARSHALL DANN Commissioner ofPatenrs and Trademarks 

1. A METHOD OF REDUCING BLOOD PRESSURE IN HYPERTENSIVE PATIENTS BY ADMINISTERING A THERAPEUTICALLY EFFECTIVE AMOUNT OF A COMPOUND OF THE FORMULA 